1. Field of the Invention
This invention relates to amino acid imide derivatives, and, more particularly, to amino acid imide derivatives possessing prolyl endopeptidase inhibitory activity, antihypoxic activity, and anti-amnesia activity, and hence are useful as a medicine for treating or preventing cerebral circulation disorder, cerebral metabolism disorder, and memory disturbance.
2. Description of the Background
Senile dementia caused by such cerebral disorders as cerebrovascular disorder, cerebral circulation disorder, cerebral metabolism disorder, and memory disturbance has become a social problem in the society with prolonged life-span. Development of medicines useful for treating or preventing these diseases are thus desired.
A recent clinical report [. F. Mazurek et al., Neurology, 36, 1133 (1986)] revealed a remarkable decrease of peptides participating in memory or neurotransmission in brains of senile dementia patients.
Prolyl endopeptidase inhibitors are known as exhibiting anti-amnesic activity, since prolyl endopeptidase hydrolyzes and inactivates neuropeptides including proline(s) in brains such as vasopressin [European Patent Publication No. 232849, Folia Pharmacologica Japonica, 89, 323 (1987), and id., 89, 243 (1987)]. It is also a clinical knowledge that a decreased oxygen supply to brain tissues caused by cerebral circulation disorder, cerebral metabolism disorder, or the like remarkably lowers the brain cell functions. The continuous decrease in oxygen supply to brain tissues is reported to inactivate physiological functions and to cause irreversible organic disorders [Folia Pharmacologica Japonica, 76, 655 (1980)]. Preventing the decreased oxygen supply to brain tissues can thus protect the failure of the brain functions.
Drugs improving cerebral circulation, cerebral vasodilators, cerebral metabolism accelerators, and the like are clinically used as medicines for treating cerebrovascular disorders. These medicines, however, exhibit only insufficient improvement in neurological symptoms or disorders of ability of dayly life in the patients, even though they are recognized to improve subjective symptoms. Therefore, development of a medicine possessing both cerebral metabolism improving effects and anti-amnesic activity based on prolyl endopeptidase inhibitory action has been desired.
The present inventors have undertaken extensive studies on various compounds in order to obtain an excellent medicine for improving cerebral circulation/metabolism and for preventing amnesia. As a result, the inventors have found that certain types of amino acid imide derivatives exhibit both prolyl endopeptidase inhibitory activity and cerebral circulation/metabolism improving activity at the same time, and hence can be an excellent medicine for improving cerebral circulation/metabolism and for treating or preventing amnesia. These findings have led to the completion of this invention.